Scientists create artificial vascular networks using sugar

For a great number of people, the idea of being able to use a patient’s own cells to create lab-grown replacement organs is very appealing. Already, researchers have had success growing urethras (which are essentially hollow tubes), and miniature human livers. Before large, solid, three-dimensional organs can be grown, however, scientists must figure out a reliable way of incorporating blood vessels into them – if the lab-grown organs simply take the form of a block of cells, the cells on the inside won’t be able to receive any nutrients, and will die. Now, a team from the University of Pennsylvania and MIT has devised a way of building such vessels, using sugar.

The scientists use a relatively inexpensive open-source RepRap 3D printer, which extrudes molten sugar – a mixture of sucrose, glucose and dextran is used, as that formulation offers strength (once the sugar hardens), plus biocompatibility with a wide range of cell types. That sugar is used to create a three-dimensional solid-sided mold that has a network of thin filaments of sugar running back and forth within it, from one side of its interior to the other. Those filaments are coated with a thin layer of a corn-derived polymer.

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A water-based gel containing organ cells is then poured into the mold, flowing around the filaments. The polymer on the filaments reacts with the gel as it’s solidifying, causing the filaments to dissolve. As the liquified sugar is flushed out of the gel, tiny tunnels in the shape of the filaments are left behind. Nutrient-rich fluids can then be pumped through those vessels, delivering nutrients to cells throughout the gel block.

A microscope image of one of the 3D-printed vascular network templates

When human blood vessel cells were injected into the artificial vascular networks, capillaries spontaneously began sprouting off of the main vessels into the surrounding gel – just like a natural vascular network grows. When liver cells were used in the gel, their production of albumin and urea increased as the nutrient fluid was introduced. Albumin and urea are found naturally in blood and urine (respectively), and their presence is an indicator of proper liver cell function. Additionally, the cells located closest to the vessels showed the highest rate of survival.

While the technology has great promise, the concentration of liver cells in the gel will need to be increased dramatically before an actual replacement liver could be produced. “The therapeutic window for human-liver therapy is estimated at one to 10 billion functional liver cells,” said MIT’s Sangeeta N. Bhatia, one of the team leaders. “With this work, we've brought engineered liver tissues orders of magnitude closer to that goal, but at tens of millions of liver cells per gel we've still got a ways to go.”

He added that they also have to determine how to attach their engineered vascular networks to those already existing within the body.

Another approach to creating lab-grown organs, known as 3D bioprinting, involves depositing two-dimensional layers of cell-containing gel one on top of the other, building these layers up into three-dimensional organs. Although vascular networks can be built into these organs, the vessels end up with structural seams running through them, which can fail under the pressure of circulating fluid. Also, certain types of cells (including liver cells) cannot survive the 3D bioprinting process.

A paper on the research was recently published in the journal Nature Materials. More information is available in the video below.